Is Equine Rhinitis Virus Associated with Inflammatory Airway Disease In

Total Page:16

File Type:pdf, Size:1020Kb

Is Equine Rhinitis Virus Associated with Inflammatory Airway Disease In IS EQUINE RHINITIS V IRUS ASSOCIATED WITH INFL AMMATORY AIRWAY DISEASE IN HO RSES? A MAJOR QUALIFYING PROJECT SUBMITTED TO THE FAC ULTY OF WORCESTER POLYTECHNIC INSTITUTE IN PARTIAL FULFILLMENT OF THE R EQUIREMENTS FOR THE DEGREE OF BACHELOR O F SCIENCE By: Brenna Pugliese (Biology/Biotechnology) Margaret Wigley (Biology/ Biotechnology) On: April 25, 2013 WPI Faculty Advisor: Jill Rulfs TCSVM Veterinary Advisor: Dr. Melissa Mazan, DVM, DACVIM Pugliese, Wigley 2 CONTENTS Table of Figures .......................................................................................................................................................................... 3 INTRODUCTION ......................................................................................................................................................................... 6 Inflammatory Airway Disease ......................................................................................................................................... 6 Virology ..................................................................................................................................................................................... 8 Bronchoaveolar Lavage .................................................................................................................................................... 16 Open Plethysmography .................................................................................................................................................... 20 Works Cited ................................................................................................................................................................................ 27 Introduction ............................................................................................................................................................................... 29 Materials and Methods .......................................................................................................................................................... 31 Bronchoalveolar Lavage .................................................................................................................................................. 31 Inclusion Criteria ................................................................................................................................................................ 32 Forced Oscillatory Mechanics ........................................................................................................................................ 32 Statistical Analysis .............................................................................................................................................................. 34 Results .......................................................................................................................................................................................... 35 Discussion ................................................................................................................................................................................... 38 Works Cited ................................................................................................................................................................................ 43 Pugliese, Wigley 3 TABLE OF FIGURES Figure 1: BAL tubing with inflation cuff (Tufts).......................................................................................................... 17 Figure 2: BAL set-up in equine patient. (Tufts) ........................................................................................................... 18 Figure 3: Bronchoalveolar cytology (1000xmag, Wright Giemsa stain). (a) An alveolar macrophage (AM) and a darkly granulated mast cell (MC) are shown in a sample from a normal horse. (b) From a horse with exercise induced pulmonary hemorrhage, a typical haemosiderin-laden macrophage (haemosiderophage HSP) and lymphocyte (L). (c) In a horse with marked small airway inflammatory disease is shown neutrophils (PMN), mast cells (MC) and an alveolar macrophage (AM). (d) An eosinophil (EOS) and alveolar macrophage in a normal horse. (e) Fibrillar mucus containing predominantly neutrophils was recovered from a horse with COPD. (Hoffman A. M., 1999). ........................................................................................................................................................................................... 19 Figure 4: Facemask and pneumotachograph on an equine patient during lung function testing. ........ 25 Figure 5: Placement of respiratory inductance bands on artificial horse. ....................................................... 25 Figure 6: Mean polymorphonuclear leukocyte, mast cell, and eosinophil count obtained from BAL fluid analysis. Black bar indicates sample mean. Control n=9, affected n=25………………………………… 34 Figure 7: Histamine challenge in Necco, an equine patient diagnosed with IAD. Linear fit performed………………………………………………………………………………………………………………………….……....37 Pugliese, Wigley 4 ACKNOWLEDGEMENTS Dr. Melissa Mazan, DVM, DACVIM Dr. Daniela Bedenice, DVM, DACVIM, DACVECC Tufts Cummings School of Veterinary Medicine Hospital for Large Animals Department of Veterinary Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis Dr. Elizabeth Ryder, A.B., M.S., Ph.D. Pugliese, Wigley 5 ABSTRACT We conducted research at Tufts Cummings School of Veterinary Medicine investigating equine rhinitis virus (ERV) as the cause of IAD exacerbations in horses. To identify patients with IAD, histamine bronchoprovocation and cytological analysis of bronchoalveolar lavage fluid (BALF) was used to quantify airway hyperreactivity and inflammation. The prevalence of ERV and other equine respiratory viruses was determined via the RT-PCR of lung fluid samples and serology of blood samples. We hope this will be a step forward in equine pulmonology. Pugliese, Wigley 6 INTRODUCTION Inflammatory airway disease (IAD) is a prevalent respiratory illness affecting young equine athletes. Much remains unknown about this disease and its clinical symptoms and causes. Though it is known that stable environment plays a major role in the development of IAD, little is known about the correlation between IAD and common respiratory viruses. We hypothesize that exacerbation/initiation of inflammatory airway disease in horses is associated with Equine Rhinitis Virus (ERV) infection. Our goal was to determine whether horses with an exacerbation of IAD had been recently infected with equine rhinitis virus or other related equine respiratory viruses. To accomplish this goal, pulmonary function testing was performed in combination with bronchoalveolar lavage to identify horses with IAD. In order to isolate identify viral pathogens, cells and fluid from bronchoalveolar samples were analyzed using polymerase chain reaction (PCR). Furthermore, blood samples were collected and processed to detect antibody response to these viral pathogens which would indicate recent exposure and/or infection. Determining an association between viral infections and IAD has larger implications for both equine and human health. IAD in an equine patient is akin to asthma in a human patient, and furthermore, human rhinovirus is known to cause exacerbation of asthma. Evidence to support the hypothesis that equine viral infections are associated with exacerbations of IAD will contribute to the understanding of respiratory disease in both equine and human populations. INFLAMMATORY AIRWAY DISEASE Respiratory disease is a problem worldwide in horses of all ages and occupation (Couetil, 2002). Older horses commonly experience respiratory problems, and a multitude of studies have been done to determine the various causes. Recently, it has become apparent that young horses also experience airway inflammation with no known cause (Hodgson, 2002). Research on respiratory problems in young horses is limited; focusing mainly on more common equine diseases in older horses. In 2002, a broad definition was applied to horses with nonspecific inflammation that were exhibiting exercise intolerance. This condition was termed inflammatory airway disease or IAD (Laurent L. Couetil, 2007). Pugliese, Wigley 7 IAD is not completely understood, as its etiology, inflammation and type of inflammatory cell are unknown (Hodgson, 2002). There is no universally accepted definition of IAD, but in general it is commonly seen in younger racehorses. In many cases the only indication of disease will be reduced exercise tolerance or poor performance. In other cases, there is chronic inflammation, mild airway obstruction, bronchitis or bronchiolitis, overproduction of mucus and the presence of cough. In most cases, there is a pool of mucus at the tracheal inlet or a continuous stream (K. J. Allen, 2006). The proposed minimum criteria for IAD diagnosis is poor performance or exercise intolerance, airway hyper-responsiveness, and/or impaired gas exchange at rest (Laurent L. Couetil, 2007). Of all the symptoms, cough is the most subjective when diagnosing IAD. In 2002, it was found that cough was only present in 38% of horses with IAD, yet 85% of horses with a cough were diagnosed with IAD (Couetil, 2002). Cough seems to be correlated with the amount of mucus production in both the upper and lower airways (Kanichi Kusano, 2008). Cough does not have to be present for diagnosis.
Recommended publications
  • Novel Picornavirus in Turkey Poults with Hepatitis, California, USA Kirsi S
    RESEARCH Novel Picornavirus in Turkey Poults with Hepatitis, California, USA Kirsi S. Honkavuori, H. L. Shivaprasad, Thomas Briese, Craig Street, David L. Hirschberg, Stephen K. Hutchison, and W. Ian Lipkin To identify a candidate etiologic agent for turkey viral loss compatible with a diagnosis of enteritis, the second hepatitis, we analyzed samples from diseased turkey most common diagnosis made in turkey poults throughout poults from 8 commercial fl ocks in California, USA, that the United States. Although we cannot with confi dence were collected during 2008–2010. High-throughput estimate the specifi c burden of TVH, its economic effects pyrosequencing of RNA from livers of poults with turkey are likely substantial; in the United States, turkey production viral hepatitis (TVH) revealed picornavirus sequences. was valued at $3.71 billion in 2007. The identifi cation of a Subsequent cloning of the ≈9-kb genome showed an organization similar to that of picornaviruses with pathogen and development of specifi c diagnostics will lead conservation of motifs within the P1, P2, and P3 genome to better understanding of the economic consequences and regions, but also unique features, including a 1.2-kb other effects of TVH. sequence of unknown function at the junction of P1 and The disease has been experimentally reproduced in P2 regions. Real-time PCR confi rmed viral RNA in liver, turkey poults by inoculation with material derived from bile, intestine, serum, and cloacal swab specimens from affected animals (1–4). A viral basis for TVH has been diseased poults. Analysis of liver by in situ hybridization presumed since its initial description in 1959 because with viral probes and immunohistochemical testing of the causative agent passed through 100-nm membranes, serum demonstrated viral nucleic acid and protein in livers was acid stable, was not affected by antimicrobial drugs, of diseased poults.
    [Show full text]
  • ICTV Code Assigned: 2011.001Ag Officers)
    This form should be used for all taxonomic proposals. Please complete all those modules that are applicable (and then delete the unwanted sections). For guidance, see the notes written in blue and the separate document “Help with completing a taxonomic proposal” Please try to keep related proposals within a single document; you can copy the modules to create more than one genus within a new family, for example. MODULE 1: TITLE, AUTHORS, etc (to be completed by ICTV Code assigned: 2011.001aG officers) Short title: Change existing virus species names to non-Latinized binomials (e.g. 6 new species in the genus Zetavirus) Modules attached 1 2 3 4 5 (modules 1 and 9 are required) 6 7 8 9 Author(s) with e-mail address(es) of the proposer: Van Regenmortel Marc, [email protected] Burke Donald, [email protected] Calisher Charles, [email protected] Dietzgen Ralf, [email protected] Fauquet Claude, [email protected] Ghabrial Said, [email protected] Jahrling Peter, [email protected] Johnson Karl, [email protected] Holbrook Michael, [email protected] Horzinek Marian, [email protected] Keil Guenther, [email protected] Kuhn Jens, [email protected] Mahy Brian, [email protected] Martelli Giovanni, [email protected] Pringle Craig, [email protected] Rybicki Ed, [email protected] Skern Tim, [email protected] Tesh Robert, [email protected] Wahl-Jensen Victoria, [email protected] Walker Peter, [email protected] Weaver Scott, [email protected] List the ICTV study group(s) that have seen this proposal: A list of study groups and contacts is provided at http://www.ictvonline.org/subcommittees.asp .
    [Show full text]
  • Evidence to Support Safe Return to Clinical Practice by Oral Health Professionals in Canada During the COVID-19 Pandemic: a Repo
    Evidence to support safe return to clinical practice by oral health professionals in Canada during the COVID-19 pandemic: A report prepared for the Office of the Chief Dental Officer of Canada. November 2020 update This evidence synthesis was prepared for the Office of the Chief Dental Officer, based on a comprehensive review under contract by the following: Paul Allison, Faculty of Dentistry, McGill University Raphael Freitas de Souza, Faculty of Dentistry, McGill University Lilian Aboud, Faculty of Dentistry, McGill University Martin Morris, Library, McGill University November 30th, 2020 1 Contents Page Introduction 3 Project goal and specific objectives 3 Methods used to identify and include relevant literature 4 Report structure 5 Summary of update report 5 Report results a) Which patients are at greater risk of the consequences of COVID-19 and so 7 consideration should be given to delaying elective in-person oral health care? b) What are the signs and symptoms of COVID-19 that oral health professionals 9 should screen for prior to providing in-person health care? c) What evidence exists to support patient scheduling, waiting and other non- treatment management measures for in-person oral health care? 10 d) What evidence exists to support the use of various forms of personal protective equipment (PPE) while providing in-person oral health care? 13 e) What evidence exists to support the decontamination and re-use of PPE? 15 f) What evidence exists concerning the provision of aerosol-generating 16 procedures (AGP) as part of in-person
    [Show full text]
  • The Encephalomyocarditis Virus
    The Encephalomyocarditis Virus The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Carocci, Margot, and Labib Bakkali-Kassimi. 2012. The encephalomyocarditis virus. Virulence 3(4): 351-367. Published Version doi:10.4161/viru.20573 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579128 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA REVIEW Virulence 3:4, 351–367; July 1, 2012; G 2012 Landes Bioscience The encephalomyocarditis virus Margot Carocci1,* and Labib Bakkali-Kassimi2 1Microbiology Immunology Department; Harvard Medical School; Boston, MA USA; 2Maisons-Alfort Laboratory for Animal Health; UMR 1161 Virology; ANSES; INRA; ENVA; Maisons-Alfort, France Keywords: EMCV, virulence, Picornavirus, Cardiovirus, encephalomyocarditis virus, pathogenesis, virulence factor Abbreviations: EMCV, encephalomyocarditis virus; FMDV, foot and mouth disease virus; TMEV, Theiler’s murine encephalitis virus; SAFV, Saffold virus; LC3, microtubule-associated protein 1 light chain 3; Cre, cis-acting replication element; IL-1β,interleukin-1β; TNFa, tumor necrosis factor a; NO, nitric oxide; iNOS, inducible nitric oxide synthase; RIG-I, retinoic acid-inducible gene 1 protein; MDA-5, melanoma differentiation-associated gene-5 The encephalomyocarditis virus (EMCV) is a small non- cardiovirus (compare classification) that is responsible, depending enveloped single-strand RNA virus, the causative agent of on the strain, for an acute fatal-poliomyelitis or a chronic not only myocarditis and encephalitis, but also neurological demyelinating disease with persistence of the virus in the central diseases, reproductive disorders and diabetes in many nervous system of the mouse (for review, see refs.
    [Show full text]
  • A Potential Drug Target for Inhibiting Virus Replication
    Old Dominion University ODU Digital Commons Chemistry & Biochemistry Theses & Dissertations Chemistry & Biochemistry Winter 2018 Structure of the Picornavirus Replication Platform: A Potential Drug Target for Inhibiting Virus Replication Meghan Suzanne Warden Old Dominion University, [email protected] Follow this and additional works at: https://digitalcommons.odu.edu/chemistry_etds Part of the Biochemistry Commons, Chemistry Commons, Epidemiology Commons, and the Physiology Commons Recommended Citation Warden, Meghan S.. "Structure of the Picornavirus Replication Platform: A Potential Drug Target for Inhibiting Virus Replication" (2018). Doctor of Philosophy (PhD), Dissertation, Chemistry & Biochemistry, Old Dominion University, DOI: 10.25777/wyvk-8b21 https://digitalcommons.odu.edu/chemistry_etds/22 This Dissertation is brought to you for free and open access by the Chemistry & Biochemistry at ODU Digital Commons. It has been accepted for inclusion in Chemistry & Biochemistry Theses & Dissertations by an authorized administrator of ODU Digital Commons. For more information, please contact [email protected]. STRUCTURE OF THE PICORNAVIRUS REPLICATION PLATFORM: A POTENTIAL DRUG TARGET FOR INHIBITING VIRUS REPLICATION by Meghan Suzanne Warden B.S. May 2011, Lambuth University A Dissertation Submitted to the Faculty of Old Dominion University in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY CHEMISTRY OLD DOMINION UNIVERSITY December 2018 Approved by: Steven M. Pascal (Director) Lesley H. Greene (Member) Hameeda Sultana (Member) James W. Lee (Member) John B. Cooper (Member) ABSTRACT STRUCTURE OF THE PICORNAVIRUS REPLICATION PLATFORM: A POTENTIAL DRUG TARGET FOR INHIBITING VIRUS REPLICATION Meghan Suzanne Warden Old Dominion University, 2018 Director: Dr. Steven M. Pascal Picornaviruses are small, positive-stranded RNA viruses, divided into twelve different genera.
    [Show full text]
  • Metagenomic Characterisation of Avian Parvoviruses And
    www.nature.com/scientificreports OPEN Metagenomic characterisation of avian parvoviruses and picornaviruses from Australian wild ducks Jessy Vibin1,2*, Anthony Chamings1,2, Marcel Klaassen3, Tarka Raj Bhatta1,2 & Soren Alexandersen1,2,4* Ducks can shed and disseminate viruses and thus play a role in cross-species transmission. In the current study, we detected and characterised various avian parvoviruses and picornaviruses from wild Pacifc black ducks, Chestnut teals, Grey teals and Wood ducks sampled at multiple time points from a single location using metagenomics. We characterised 46 diferent avian parvoviruses belonging to three diferent genera Dependoparvovirus, Aveparvovirus and Chaphamaparvovirus, and 11 diferent avian picornaviruses tentatively belonging to four diferent genera Sicinivirus, Anativirus, Megrivirus and Aalivirus. Most of these viruses were genetically diferent from other currently known viruses from the NCBI dataset. The study showed that the abundance and number of avian picornaviruses and parvoviruses varied considerably throughout the year, with the high number of virus reads in some of the duck samples highly suggestive of an active infection at the time of sampling. The detection and characterisation of several parvoviruses and picornaviruses from the individual duck samples also suggests co-infection, which may lead to the emergence of novel viruses through possible recombination. Therefore, as new and emerging diseases evolve, it is relevant to explore and monitor potential animal reservoirs in their natural habitat. Birds and other animals can be reservoirs for zoonotic viruses that may have serious implications for human health and agriculture, for example, avian infuenza A virus1 or severe acute respiratory syndrome coronavirus2. Among birds, notably wild ducks constitute a signifcant reservoir for viruses including, but not limited to, infu- enza viruses3,4 and coronaviruses5,6.
    [Show full text]
  • Multiple Types of Novel Enteric Bopiviruses (Picornaviridae)
    viruses Article Multiple Types of Novel Enteric Bopiviruses (Picornaviridae) with the Possibility of Interspecies Transmission Identified from Cloven-Hoofed Domestic Livestock (Ovine, Caprine and Bovine) in Hungary Zoltán László 1,Péter Pankovics 1,Gábor Reuter 1, Attila Cságola 2, Ádám Bálint 3, Mihály Albert 2 and Ákos Boros 1,* 1 Department of Medical Microbiology and Immunology, Medical School, University of Pécs, H-7624 Pécs, Hungary; [email protected] (Z.L.); [email protected] (P.P.); [email protected] (G.R.) 2 Ceva Phylaxia Ltd., H-1107 Budapest, Hungary; [email protected] (A.C.); [email protected] (M.A.) 3 Department of Virology, National Food Chain Safety Office Veterinary Diagnostic Directorate, H-1143 Budapest, Hungary; [email protected] * Correspondence: [email protected]; Tel.: +36-72-536-251 Abstract: Most picornaviruses of the family Picornaviridae are relatively well known, but there are certain “neglected” genera like Bopivirus, containing a single uncharacterised sequence (bopivirus A1, KM589358) with very limited background information. In this study, three novel picornaviruses provisionally called ovipi-, gopi- and bopivirus/Hun (MW298057-MW298059) from enteric samples of asymptomatic ovine, caprine and bovine respectively, were determined using RT-PCR and dye- Citation: László, Z.; Pankovics, P.; terminator sequencing techniques. These monophyletic viruses share the same type II-like IRES, Reuter, G.; Cságola, A.; Bálint, Á.; NPGP-type 2A, similar genome layout (4-3-4) and cre-localisations. Culture attempts of the study Albert, M.; Boros, Á. Multiple Types of Novel Enteric Bopiviruses viruses, using six different cell lines, yielded no evidence of viral growth in vitro.
    [Show full text]
  • Rna Viral Diversity and Dynamics Along the Antarctic Peninsula
    RNA VIRAL DIVERSITY AND DYNAMICS ALONG THE ANTARCTIC PENINSULA A DISSERTATION SUBMITTED TO THE GRADUATE DIVISION OF THE UNIVERSITY OF HAWAIʻI AT MĀNOA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN OCEANOGRAPHY MAY 2015 By Jaclyn A. Mueller Dissertation Committee: Grieg Steward, Chairperson Alexander Culley Matthew Church Craig Smith Guylaine Poisson, Outside member Key words: marine RNA viruses, viral ecology, metagenomes, viromes, nucleic acid extraction, reverse transcription quantitative PCR (RT-qPCR), Antarctica © Copyright 2015 – Jaclyn A Mueller All rights reserved. ii ACKNOWLEDGEMENTS This research would not have been possible without the generosity and support of a number of people and organizations, for which I am very thankful. I would first like to acknowledge the Department of Oceanography, the Center for Microbial Oceanography: Research and Education (C-MORE), and the National Science Foundation (NSF) for supporting my research and providing such a fulfilling and enriching graduate career. I am forever indebted to the C-MORE ‘Ohana for their unwavering support and enthusiasm, while providing me the opportunity to experience outreach and education, enhance my leadership and professional development skills, and conduct my doctoral research. In particular, I thank Dr. David Karl for his insights, enthusiasm for oceanography, and continued support of my research. It has been a pleasure to work with so many bright, motivated, and inspiring scientists. I am forever grateful for the patience, guidance, encouragement, and support of my advisor, Dr. Grieg Steward. His enthusiasm and creativity are contagious, and have made this experience quite an enjoyable one. Working with him has not only taught me to be more a perceptive and critical thinker, but also a better writer and scientist.
    [Show full text]
  • A Highly Prevalent and Genetically Diversified Picornaviridae Genus in South Asian Children
    A highly prevalent and genetically diversified Picornaviridae genus in South Asian children Amit Kapoora,b, Joseph Victoriaa,b, Peter Simmondsc, Elizabeth Slikasa,b, Thaweesak Chieochansinc, Asif Naeemd, Shahzad Shaukatd, Salmaan Sharifd, Muhammad Masroor Alamd, Mehar Angezd, Chunlin Wange,f, Robert W. Shafere, Sohail Zaidid, and Eric Delwarta,b,1 aBlood Systems Research Institute, San Francisco CA 94118; bDepartment of Laboratory Medicine, University of California, San Francisco, CA 94118; cCentre for Infectious Diseases, University of Edinburgh, Edinburgh EH9 1QH, United Kingdom; dDepartment of Virology, National Institute of Health, Islamabad, Pakistan; eDivision of Infectious Diseases, Stanford University Medical Center, Stanford, CA 94305; and fStanford Genome Technology Center, Stanford, CA 94304 Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved October 16, 2008 (received for review August 13, 2008) Viral metagenomics focused on particle-protected nucleic acids for reverse transcription, Klenow fragment DNA polymerase was used on the stools of South Asian children with nonpolio acute extension, and PCR. Amplified DNA libraries where then sub- flaccid paralysis (AFP). We identified sequences distantly related to cloned and shotgun-sequenced (see Materials and Methods). A Seneca Valley virus and cardioviruses that were then used as stool sample showed the presence of multiple nucleic acids genetic footholds to characterize multiple viral species within a fragments whose in silico translation products were distantly previously unreported genus of the Picornaviridae family. The related to Seneca Valley virus (SVV)- and cardiovirus-encoded picornaviruses were detected in the stools of >40% of AFP and proteins. These initial picornavirus-like fragments were joined healthy Pakistani children.
    [Show full text]
  • A Highly Prevalent and Genetically Diversified Picornaviridae Genus in South Asian Children
    A highly prevalent and genetically diversified Picornaviridae genus in South Asian children Amit Kapoora,b, Joseph Victoriaa,b, Peter Simmondsc, Elizabeth Slikasa,b, Thaweesak Chieochansinc, Asif Naeemd, Shahzad Shaukatd, Salmaan Sharifd, Muhammad Masroor Alamd, Mehar Angezd, Chunlin Wange,f, Robert W. Shafere, Sohail Zaidid, and Eric Delwarta,b,1 aBlood Systems Research Institute, San Francisco CA 94118; bDepartment of Laboratory Medicine, University of California, San Francisco, CA 94118; cCentre for Infectious Diseases, University of Edinburgh, Edinburgh EH9 1QH, United Kingdom; dDepartment of Virology, National Institute of Health, Islamabad, Pakistan; eDivision of Infectious Diseases, Stanford University Medical Center, Stanford, CA 94305; and fStanford Genome Technology Center, Stanford, CA 94304 Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved October 16, 2008 (received for review August 13, 2008) Viral metagenomics focused on particle-protected nucleic acids for reverse transcription, Klenow fragment DNA polymerase was used on the stools of South Asian children with nonpolio acute extension, and PCR. Amplified DNA libraries where then sub- flaccid paralysis (AFP). We identified sequences distantly related to cloned and shotgun-sequenced (see Materials and Methods). A Seneca Valley virus and cardioviruses that were then used as stool sample showed the presence of multiple nucleic acids genetic footholds to characterize multiple viral species within a fragments whose in silico translation products were distantly previously unreported genus of the Picornaviridae family. The related to Seneca Valley virus (SVV)- and cardiovirus-encoded picornaviruses were detected in the stools of >40% of AFP and proteins. These initial picornavirus-like fragments were joined healthy Pakistani children.
    [Show full text]
  • 1 Disclosure 2 Defining Our Terms 3 Meningitis 4 Encephalitis 5 Myelitis 6
    5/5/20 Disclosure Solving Neurologic Mysteries: Next-Generation Approaches to Diagnosis Michael Wilson, MD, MAS Associate Professor UCSF Weill Institute for Neurosciences Department of Neurology Division of Neuroimmunology and Glial Biology 1 2 Defining Our Terms Meningitis • Meningitis: inflammation of the meninges • Encephalitis: inflammation of the brain • Myelitis: inflammation of the spinal cord 3 4 Encephalitis Myelitis 5 6 1 5/5/20 Meningoencephalitis Encephalitis: Morbidity and Mortality • ~20,000 cases/year in the United States • $2 billion in inpatient costs • ~10% mortality • Survivors are frequently disabled – speech, memory, mobility 7 8 Encephalitis of Unknown Etiology Diagnostic Challenges • > 50% unknown cases in 26 of 41 studies in recent meta-analysis • > 100 pathogens cause encephalitis • Not explained by # of pathogens tested for • Wide variation • California Encephalitis Project • Geography • 7 years (1,570 cases): 63% of cases unknown • Season • Patient demographic • Epidemics • Granerod J, et al. Neurology 2010;75:924-932 • Glaser CA, et al. CID 2006;43:1565-1577 9 10 Emerging Neurologic Infections Zika Virus • West Nile virus • Phylogenetic analyses indicate Zika was introduced to BraZil in 2013 • Periodic measles, mumps outbreaks • Chikungunya virus • 18 months before it was detected • Zika virus • Powassan virus • Nearly 2 years before recogniZed as a cause of microcephaly, • Nipah and Hendra viruses meningoencephalitis and Guillain-Barré syndrome • Enterovirus A71 • Chandipura virus • Monkeypox virus • Ebola virus • PML in HIV and other immunosuppressed patients • Rate of severe neurological symptoms caused by emerging viruses • Arenavirus (LCMV-like) in solid organ transplant pts • 39% commonly do so • Dengue virus in the Florida Keys • 10% rarely or occasionally do so • ? SARS-Coronavirus-2 ? • Lipkin WI.
    [Show full text]
  • Viral Security Proteins: Counteracting Host Defences
    REVIEWS Viral security proteins: counteracting host defences Vadim I. Agol*‡ and Anatoly P. Gmyl* Abstract | Interactions with host defences are key aspects of viral infection. Various viral proteins perform counter-defensive functions, but a distinct class, called security proteins, is dedicated specifically to counteracting host defences. Here, the properties of the picornavirus security proteins L and 2A are discussed. These proteins have well-defined positions in the viral polyprotein, flanking the capsid precursor, but they are structurally and biochemically unrelated. Here, we consider the impact of these two proteins, as well as that of a third security protein, L*, on viral reproduction, pathogenicity and evolution. The concept of security proteins could serve as a paradigm for the dedicated counter-defensive proteins of other viruses. All bona fide RNA viruses encode at least two proteins, a positive-sense RNA genome (BOX 1). Although they share capsid protein and an RNA-dependent RNA polymerase a common genome organization, these viruses exhibit (RdRP). In this article, we do not consider ‘abnormal’ sufficient genetic variation to be separated into at least RNA viruses such as hepatitis delta virus, which does 12 distinct genera (BOX 2). The family includes impor- not possess its own replication machinery and borrows tant human and animal pathogens that cause a range a capsid from another virus1, or the capsid-less narna- of disorders, including poliomyelitis, foot-and-mouth viruses, which encode only an RdRP2; hepatitis delta disease, the common cold, gastroenteritis, hepatitis, virus and narnaviruses are closer to viroids and plas- meningitis, myocarditis and uveitis. In addition to acute mids, respectively, than to fully fledged RNA viruses.
    [Show full text]